<b><i>Aims:</i></b> To explore previously unreported rates and trends in opioid-related mortality in Israel, 2005–2014. <b><i>Methods:</i></b> Data was obtained from the national database on causes of death. Drug poisoning deaths were divided into opioid-related deaths and deaths related to other drugs according to International Classification of Diseases (ICD)-10 code of underlying cause, and included drug poisoning of accidental, intentional or undetermined intent. Age-adjusted rates were calculated per 100,000 population. Rate ratios were calculated and a logistic model constructed to compare the risk of opioid-related deaths in both halves of the decade (2006–2009 and 2009–2013) and between various demographic groups. <b><i>Results:</i></b> While age-adjusted rates of deaths related to other drugs remained relatively stable, rates of opioid-related deaths significantly decreased during this period across all groups. During the study period, the number of opioid-related deaths in Israel declined from 1.3 to 0.3 per 100,000. Opioid-related deaths were more common among men, young adults and immigrants from the Former Soviet Union.<b><i> Conclusions:</i></b> Rates of opioid-related deaths in Israel were low compared to those reported in the United States and United Kingdom. In addition, the decline in opioid-related deaths in Israel is contrary to trends observed in the United States and United Kingdom. Factors that may contribute to these differences are discussed.